Research Paper Volume 10, Issue 12 pp 3761—3773

DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation

Scott J. Morin 1, 2, , Xin Tao 3, , Diego Marin 1, 2, , Yiping Zhan 3, , Jessica Landis 3, , Jenna Bedard 3, , Richard T. Scott Jr. 1, 2, , Emre Seli 1, 4, ,

  • 1 IVIRMA New Jersey, Basking Ridge, NJ 07920, USA
  • 2 Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
  • 3 Foundation for Embryonic Competence, Basking Ridge, NJ 07920, USA
  • 4 Yale School of Medicine, New Haven, CT 06510, USA

received: October 5, 2018 ; accepted: November 15, 2018 ; published: December 8, 2018 ;

https://doi.org/10.18632/aging.101670
How to Cite

Copyright: Morin et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

An algorithm assessing the methylation levels of 353 informative CpG sites in the human genome permits accurate prediction of the chronologic age of a subject. Interestingly, when there is discrepancy between the predicted age and chronologic age (age acceleration or “AgeAccel”), patients are at risk for morbidity and mortality. Identification of infertile patients at risk for accelerated reproductive senescence may permit preventative action. This study aimed to assess the accuracy of the “epigenetic clock” concept in reproductive age women undergoing fertility treatment by applying the age prediction algorithm in peripheral (white blood cells [WBCs]) and follicular somatic cells (cumulus cells [CCs]), and to identify whether women with premature reproductive aging (diminished ovarian reserve) were at risk of AgeAccel in their age prediction. Results indicated that the epigenetic algorithm accurately predicts age when applied to WBCs but not to CCs. The age prediction of CCs was substantially younger than chronologic age regardless of the patient’s age or response to stimulation. In addition, telomeres of CCs were significantly longer than that of WBCs. Our findings suggest that CCs do not demonstrate changes in methylome-predicted age or telomere-length in association with increasing female age or ovarian response to stimulation.

Abbreviations

CC: cumulus cells; WBC: white blood cells; TL: telomere length; Ct: cycle threshold; DOR: diminished ovarian reserve; IVF: in vitro fertilization; ART: assisted reproductive technology; WHI: Women’s Health Initiative; FHS: Framingham Heart Study; COS: controlled ovarian stimulation; AMH: anti-Müllerian hormone; BMI: body mass index; COC: cumulus-oocyte complexes; 2PN: 2 pronuclei; E2: Estradiol; FSH: Follicle stimulating hormone; LH: Luteinizing hormone; GnRH: Gonadotropin releasing hormone.